Akt2 expression is associated with good long-term prognosis in estrogen receptor positive breast cancer.

Introduction: Akt is a signaling modulator for many cellular processes, including metabolism, cell proliferation, cell survival and cell growth. Three isoforms of Akt have been identified, but only a few studies have concerned the isoform-specific roles in the prognosis of breast cancer patients. The aim of this study was to investigate the prognostic value of Akt1 and Akt2 in estrogen receptor positive (ER+) and estrogen receptor negative (ER-) breast cancer with long-term follow-up. Material and Methods: The expression of Akt in tumor tissue was analyzed with immunohistochemistry in a cohort of 272 postmenopausal patients with stage II breast cancer. Hazard ratios and 95% confidence intervals were estimated using the Cox's proportional hazards model. Results: The risk of distant recurrence was reduced for patients with ER+ tumors expressing Akt2 compared to patients with no Akt2 expression (HR = 0.49, 95% Cl 0.29-0.82, p = 0.007). When adjusting for important clinical tumor characteristics and treatment, Akt2 was still an independent prognostic factor (HR = 0.38, 95% Cl 0.21-0.68, p = 0.001) and the association remained long-term. After more than five years since diagnosis the risk reduction was 57% for patients with Akt2 positive tumors. The prognostic value of Akt2 increased with higher estrogen receptor levels from no effect among patients with ER-tumors to 68% risk reduction for the group with high ER-levels (P for trend= 0.042). Akt1 showed no significant prognostic information. Conclusion: Our results indicate that Akt2 expression is associated with a lower distant recurrence rate for patients with ER+ tumors and that this association remains long-term. The prognostic value of Akt2 increases with higher estrogen receptor expression, motivating further mechanistic studies on the role of Akt2 in ER+ breast cancer. [ABSTRACT FROM AUTHOR]